Project Summary: Sexually transmitted infections (STIs) are highly prevalent among adolescents. Despite established principles for STI control, clinical practices related to screening and diagnosis, treatment, and prevention of STIs among adolescents are suboptimal. There is an urgent need to expand our screening programs to nontraditional healthcare settings such as emergency departments (ED) to reach those adolescents who would otherwise not receive preventive healthcare, and to determine the most efficient and cost-effective method for providing this screening. The goal of this application is to leverage our recent insights obtained from single center ED-based adolescent gonorrhea and chlamydia screening research and apply them across a national pediatric ED research network to determine the most clinically effective and cost-effective screening approach for adolescents when implemented into a real-world clinical setting through a pragmatic trial. This will be accomplished through a network of children?s hospital EDs with a track record of robust research collaboration (Pediatric Emergency Care Applied Research Network or PECARN). This research will contribute to the evidence base for creating clinically effective, cost-effective, and sustainable GC/CT screening programs that can be successfully implemented into the clinical workflow of the ED. It will also improve diagnosis of asymptomatic STIs and decrease the time interval to treatment, consequently decreasing reinfection rates of transmission and the overall STI burden as well as decreasing healthcare costs. This intervention will rely on an innovative approach that electronically integrates patient-reported data to guide clinical decision support. This work is significant because it has the potential to shift current ED clinical practice paradigms from only acute health encounters to participation in the broader management of public health, and it will fill gaps in the literature needed to provide evidence for the best method of gonorrhea and chlamydia screening in an ED setting. First, we will apply human factors modeling methods to perform ED workflow evaluations at each participating pediatric ED to determine the most efficient way to integrate the screening process into everyday clinical care. Following these analyses, we will conduct a comparative effectiveness pragmatic trial of targeted STI screening (screening only those disclosing high risk sexual behavior) versus universally-offered STI screening (offered to all, regardless of risk) through electronic integration of patient reported data for provision of clinical decision support. We will then develop decision analytic models to evaluate the cost-effectiveness of targeted screening compared to universally offered screening. This research is novel in that it shifts the usual clinical practice paradigm in the ED from STI diagnosis in symptomatic adolescents to STI screening and prevention, an approach that is critical to addressing the STI epidemic among adolescents.